In situ mantle cell lymphoma: clinical implications of an incidental finding with indolent clinical behavior

Background Cyclin D1-positive B cells are occasionally found in the mantle zones of reactive lymphoid follicles, a condition that has been called 'in situ mantle cell lymphoma'. The clinical significance of this lesion remains uncertain. Design and Methods The clinical and pathological characteristics, including SOX11 expression, of 23 cases initially diagnosed as in situ mantle cell lymphoma were studied. Results Seventeen of the 23 cases fulfilled the criteria for in situ mantle cell lymphoma. In most cases, the lesions were incidental findings in reactive lymph nodes. The t(11; 14) was detected in all eight cases examined. SOX11 was positive in seven of 16 cases (44%). Five cases were associated with other small B-cell lymphomas. In two cases, both SOX11-positive, the in situ mantle cell lymphoma lesions were discovered after the diagnosis of overt lymphoma; one 4 years earlier, and one 3 years later. Twelve of the remaining 15 patients had a follow-up of at least 1 year (median 2 years; range, 1-19.5), of whom 11 showed no evidence of progression, including seven who were not treated. Only one of 12 patients with an in situ mantle cell lymphoma lesion and no diagnosis of mantle cell lymphoma at the time developed an overt lymphoma, 4 years later; this case was also SOX11-positive. The six remaining cases were diagnosed as mantle cell lymphoma with a mantle zone pattern. Five were SOX11-positive and four of them were associated with lymphoma without a mantle zone pattern. Conclusions In situ mantle cell lymphoma lesions are usually an incidental finding with a very indolent behavior. These cases must be distinguished from mantle cell lymphoma with a mantle zone pattern and overt mantle cell lymphoma because they may not require therapeutic intervention

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2•72 (95% uncertainty interval [UI] 2•66–2•79) in 2000 to 2•31 (2•17–2•46) in 2019. Global annual livebirths increased from 134•5 million (131•5–137•8) in 2000 to a peak of 139•6 million (133•0–146•9) in 2016. Global livebirths then declined to 135•3 million (127•2–144•1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2•1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27•1% (95% UI 26•4–27•8) of global livebirths. Global life expectancy at birth increased from 67•2 years (95% UI 66•8–67•6) in 2000 to 73•5 years (72•8–74•3) in 2019. The total number of deaths increased from 50•7 million (49•5–51•9) in 2000 to 56•5 million (53•7–59•2) in 2019. Under-5 deaths declined from 9•6 million (9•1–10•3) in 2000 to 5•0 million (4•3–6•0) in 2019. Global population increased by 25•7%, from 6•2 billion (6•0–6•3) in 2000 to 7•7 billion (7•5–8•0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58•6 years (56•1–60•8) in 2000 to 63•5 years (60•8–66•1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation: Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

The effect of internship dimensions on the experience of De La Salle University Bachelor of science in accountancy students

Internships are crucial for college students, providing practical field exposure and skill refinement. The study examined the effect of internship dimensions of De La Salle University Bachelor of Science in Accountancy Students on their internship experience. Specifically, the study looked into the effect of Skill Variety, Task Identity, Task Significance, Task Autonomy, and feedback from the job on their internship experiences. The top four accounting firms were selected for insights based on intern participation. Data was collected from 95 respondents through a survey modeled on Hackman & Oldham\u27s Job Diagnostic Survey. Statistical methods included regression, assumption tests, correlation, and descriptive analysis. The findings show that only task significance and feedback from the job significantly affect internship experience (p = .0298; p = .0034). However, partial slope estimates are relatively low (task significance = .1807; feedback from the job = 0.2792). This means a one-unit increase in task significance relates to a 0.1807 increase in perceived work meaningfulness. Similarly, a one-unit feedback increase yields a 0.2792 knowledge increase in work outcomes. This underscores that a positive internship experience BSA interns hinges on perceiving assigned tasks as impactful to others within and outside the firm and receiving substantial feedback on their contributions

Bromatological characteristics of fillet fish of Leporinus agassizi and Leporinus fasciatus (Pisces: Characidae) in its natural habitat

Se analizaron los parámetros bromatológicos de 39 filetes de Warakú verdadero (Leporinus agassizi) y 21 filetes de Warakú pinima (Leporinus fasciatus) muestreados durante un ciclo hidrológico en tres puntos diferentes del Rio Vaupés, Colombia. Los parámetros evaluados no presentaron diferencias significativas en relación al sitio y época de captura. En el punto 3 y durante la temporada de aguas descendentes Leporinus agassizi tuvo los valores más altos para materia seca (25,24%), proteína (19,82%) y cenizas (2,16%). Los mayores niveles de lípidos para esta especie fueron encontrados en aguas bajas del punto 1 (2,93%). Leporinus fasciatus presentó los niveles más altos de materia seca (25,19%) y cenizas (2,16%) en el punto 3 durante la temporada de aguas ascendentes y altas, respectivamente. Las variables bromatológicas tendieron a variar de acuerdo con la época del año. Fue posible determinar que estas especies de peces poseen un gran potencial para la acuicultura de aguas continentales constituyendo así un modelo de alimentación saludable

Características bromatológicas de filetes de Leporinus agassiz y Leporinus fasciatus(Pisces: Characidae) en su hábitat natural

Bromatological parameters in 39 Warakú verdadero (Leporinus agassizi) and 21 Warakú pinima (Leporinus fasciatus) fillets were analyzed at three different sites of the Vaupés River, Colombia sampled during a hydrobiological cycle. The bromatological parameters did not shown significant differences in relation to the sites and season of capture. At point 3 and during the descending water season Leporinus agassizi had the highest values for dry matter (25.24%), protein (19.82%) and ash (2.16%). The highest lipid value for this species was found in low waters at point 1 (2.93%). Leporinus fasciatus showed the highest levels of dry matter (25.19%) and ash (2.16%) at point 3 during ascendant and high waters, respectively. The bromatological parameters tends to vary regarding the time of year. It was possible to determined that these fish species have great potential for continental aquaculture thus constituting a healthy food model.Se analizaron los parámetros bromatológicos de 39 filetes de Warakú verdadero (Leporinus agassizi) y 21 filetes de Warakú pinima (Leporinus fasciatus) muestreados durante un ciclo hidrológico en tres puntos diferentes del Rio Vaupés, Colombia. Los parámetros evaluados no presentaron diferencias significativas en relación al sitio y época de captura. En el punto 3 y durante la temporada de aguas descendentes Leporinus agassizi tuvo los valores más altos para materia seca (25,24%), proteína (19,82%) y cenizas (2,16%). Los mayores niveles de lípidos para esta especie fueron encontrados en aguas bajas del punto 1 (2,93%). Leporinus fasciatus presentó los niveles más altos de materia seca (25,19%) y cenizas (2,16%) en el punto 3 durante la temporada de aguas ascendentes y altas, respectivamente. Las variables bromatológicas tendieron a variar de acuerdo con la época del año. Fue posible determinar que estas especies de peces poseen un gran potencial para la acuicultura de aguas continentales constituyendo así un modelo de alimentación saludable